[unreadable] The long-range goal of the proposed research is to understand at the molecular level how interactions between the cell surface receptor, CD44, and its principal ligand, hyaluronic acid (HA), modulate cellular functions such as cell adhesion and migration. This understanding is critical because CD44-HA interactions play important roles in normal cell function, inflammatory response, and tumor cell invasion and metastasis. The first step toward this goal is to solve the structure of the extracellular binding domain of CD44. Residues known from mutagenesis to be important for HA binding will be mapped onto the structure, revealing structure-function relationships. Subsequently, chemical shift perturbation mapping and isothermal titration calorimetry measurements will be performed using HA fragments of increasing length to illustrate how the CD44-HA binding interaction changes to accommodate ligands of varying size. The synthesis of the structural and thermodynamic information will yield insight into the mechanism of CD44-HA interactions at the molecular level. [unreadable] [unreadable]